OPINION published: 11 September 2020 doi: 10.3389/fneur.2020.01003 The Role of Echocardiography Screening at the Stroke Unit Jorge Pagola 1,2*, Carlos Pagola 3 , Jesús Juega 1,2 , Teresa González-Alujas 4 , José Alvarez-Sabin 1,2 and Carlos A. Molina 1,2 1 Stroke Unit, Neurology Department, Vall D’Hebron Hospital, Vall D’Hebron Research Institute, Barcelona, Spain, 2 Departament de Medicina, Universitat Autònoma Barcelona, Barcelona, Spain, 3 Cardiology Department, Ciudad de Jaén University Hospital, Jaén, Spain, 4 Echocardiography Lab Cardiology Department, Vall D’Hebrón Hospital, CIBER-CV, Barcelona, Spain Keywords: echocar diography, strain, PFO, TTE, POCUS, ventricle akinesia, cryptogenic stroke, complex aortic plaque INTRODUCTION Cardioembolic stroke is the most disabling cause of stroke and accounts for 30% of ischemic strokes (1, 2). The diagnosis is based on the identification of a potential cardiac source of embolism (SOE) (3). Transthoracic Echocardiogram (TTE) is a non-invasive, available and easy to perform technique to detect SOE with potential therapeutic implications (4, 5). The therapeutic yield of the TTE ranges from 2 to 37.2% depending on the age of the patients and previous heart disease (6, 7). A Edited by: normal TTE decreases the yield of other advances techniques to detect SOE such as transesophageal Blanca Fuentes, echocardiogram (TEE) (8). TTE has been increasingly performed as part of stroke workup in the University Hospital La Paz, Spain past few years, whereas TEE is used infrequently as screening test (9). More recently, Point of Care Reviewed by: UltraSound (POCUS) concept has increased its field of application and TTE as a screening method Theodoros Karapanayiotides, at the Stroke Unit is certainly under this rationale (10). Aristotle University of Thessaloniki, Greece Elsa Azevedo, SUBSECTIONS RELEVANT FOR THE SUBJECT Centro Hospitalar Universitário de São João (CHUSJ) Dep, Portugal The most frequent SOE are: atrial fibrillation (AF), left ventricle (LV) thrombus, endocarditis, *Correspondence: prosthetic valves, and patent foramen ovale (PFO) (11). TTE contributes to the detection of these Jorge Pagola cardiac SOE as described below: jpagola@vhebron.net TTE—Atrial Fibrillation and Atrial Dysfunction Specialty section: Every patient who has AF should undergo TTE study to find out the cause of the arrhythmia, which This article was submitted to may range from non-cardiac causes (hyperthyroidism, alcoholism) to structural changes involving Stroke, left atrial (LA) mitral stenosis. TTE will be of use in patients with previous AF and stroke to rule a section of the journal out subjacent valvular disease before the initiation of direct oral anticoagulants. Additionally, in Frontiers in Neurology cases of early recurrent embolism whether atrial thrombus is suspected. However, TTE has some Received: 12 May 2020 difficulty evaluating the LA appendage where a thrombus may be lodged, although the development Accepted: 30 July 2020 of real-time three-dimensional TTE can interrogate the LA appendage (12, 13). Published: 11 September 2020 It is unsustainable to provide prolonged monitoring to all patients. TTE can help select patients Citation: at risk of latent AF by the measurement of atrial dysfunction surrogates. Increased left atrial volume Pagola J, Pagola C, Juega J, by TTE is one of these markers (14–16). Other TTE parameter related to development of AF is left González-Alujas T, Alvarez-Sabin J and Molina CA (2020) The Role of atrial strain that assesses the left atria distensibility (17). Echocardiography Screening at the In recent years, the role of atrial dysfunction and atrial remodeling are being discussed as risk Stroke Unit. Front. Neurol. 11:1003. factors for further stroke in patients without AF. Accordingly, patients with severe LA enlargement doi: 10.3389/fneur.2020.01003 (indicating atrial remodeling) are at risk of further ischemic stroke despite aspirin (18). Frontiers in Neurology | www.frontiersin.org 1 September 2020 | Volume 11 | Article 1003 Pagola et al. POCUS Enhances Cardioembolic Stroke Detection TTE—Left Ventricular Thrombus and Left has a cerebral hematoma, TTE may be useful to monitor the Ventricular Dysfunction functionality of the prosthesis till the anticoagulants are resumed. The second most prevalent cause of cardioembolic stroke is LV Degenerative or rheumatic mitral stenosis can be detected with akinesia related or not to LV thrombus (19, 20). TTE will easily TTE and Doppler gradient by evaluating the thickening and the detect LV akinesia of cardiac apex and anterior wall with 96% lack of mobility of the valves. In both native and mechanical sensitivity and 90% specificity (21). The use of echocontrast can valvulopathies, infective endocarditis is a possible cause of improve the visualization of hyperechogenic mass in at least two stroke. TTE plays a central role in detection of endocarditis; orthogonal views of an akinetic area (LV thrombus) (22). In however, when suspected TEE is mandatory to determine the addition, TTE can detect silent ischemic cardiopathy in patients valve involvement and the characteristics of the vegetations with subclinical coronary disease who will require the attention (35). Equally, in order to diagnose non-bacterial thrombotic of cardiologists. endocarditis (marantic endocarditis) TEE must be performed Systolic dysfunction with EF < 30% is simply detectable with rather than TTE that may underdetect the vegetations (36). conventional software of TTE (Simpson formulae) and it is Valvular and annular calcifications are associated with cover frequently associated with dilated cardiomyopathy (23). brain infarcts and cognitive decline (37). Some cases of embolization has been observed in mitral caseous degeneration TTE—PFO and Other Interatrial Changes that is detected by TTE as a large echogenic mass with a central In young patients with cryptogenic stroke and a high Risk of echo-lucent area (38). Additionally, detection of aortic stenosis Paradoxical Embolism (RoPE) score the presence of a PFO must will be important to follow due to its poor prognosis in the be evaluated (24). TTE may detects certain normal anatomic long term. variations of cardiac structures that may favor the formation of thrombi (25). The aneurysm of the interatrial septum, defined as TTE and Other Infrequent Causes >11 mm to >15 mm septum protrusion, is frequently associated Cardiac tumors are a classic SOE. However, their frequency is so with larger PFO (>4 mm size) and increases the risk of further low (< 0.3%) that, in a suspicious image, we must first rule out stroke (26, 27). Other structures such as the persistence of the the possibility of an artifact (some artifacts are only visualized Eustachian valve that directs the blood flow to the PFO are in one plane but not in others) or, more rarely, a thrombus. visualized with ultrasound by contrast injection (28). Both thrombi and tumors have an erratic movement, unlike the The Chiari’s network is a persistence of a remnant of cardiac structures (false tendons and trabeculations). When the the atrium formation that has been associated with thrombus movement is erratic the study should always be completed with creation (29). Finally, in patients with right atrial enlargement, TEE, and in many cases with cardiac MRI. Cardiac tumors most interatrial communication may be suspected (30). frequently associated with stroke are myxoma and fibroelastoma. Myxoma accounts for more than 50% of tumors (39). Its most TTE and Aortic Plaques common location is in the left atrium, while fibroelastoma is Complex aortic plaque is a frequent cause of cryptogenic stroke usually located in the aortic valve (40). in older patients (31, 32). Although TEE is the ultrasound If we perform TTE in the first hours after the stroke, we can modality of choice for the detection of aortic arch atheromatosis, detect transient apical dyskinesia (Tako-tsubo cardiomyopathy). many patients do not tolerate the test or they do not meet the In order to be distinguished from ventricular akinesia by TTE cardiologist’s criteria for TEE. Aortic CT is a good alternative but one should observe a wall motion abnormality not restricted to it is not ideal to evaluate mobile thrombi (12). The aortic arch a single coronary artery territory, affecting the mid-ventricular may be rapidly assessed in many patients with TTE from the portions of the anterior, inferior, and lateral walls, in a suprasternal window (33). If a plaque larger than 4 mm size or circumferential configuration (41). mobile is detected the TEE can be performed earlier and focused Non-compacted cardiomyopathy is an uncommon cause on the area of greatest suspicion. of stroke that is usually associated with systolic ventricular dysfunction (42). However, in initial stages it can cause TTE and Valvulopathies embolisms without affecting the systolic function and should be The prevalence of mitral stenosis secondary to rheumatic suspected in case of multiple trabeculations with intertrabecular valvulopathies remains a major public health concern in low and spaces in LV. In this case, once suspicion is made by TTE a middle-income countries (34). However, in our environment cardiac MRI must confirm the diagnosis. rheumatic valvulopathies has decreased dramatically and degenerative mitral stenosis related to older patients is the most common cause. The global prevalence of mitral stenosis POINT OF CARE ULTRASOUND TO has fallen and it is more common to find a patient with a ASSESS SOE mechanical prosthesis who has a stroke than a patient with classic mitral stenosis. After a stroke the chance of prosthetic In the last years, several protocols are being implemented to valve thrombosis must be assessed. Mobility of the disks and enhance the cost-effectiveness of TTE. One approach that will transvalvular gradient could be evaluated by TTE; but in order to not require any advanced tools is Point of care ultrasound rule out non-obstructive thrombosis TEE must be performed. In (POCUS). POCUS concept can be applied to the screening a different scenario, when a patient with mechanical prosthesis method of focused TTE on SOE detection, in neurologist’s Frontiers in Neurology | www.frontiersin.org 2 September 2020 | Volume 11 | Article 1003 Pagola et al. POCUS Enhances Cardioembolic Stroke Detection hands it decreased the length of stay and healthcare costs (43, In the first step of the screening with POCUS (Figure 1), 44). Indeed, a consensus Document on the recommendations viewing the ventricle, ventricular akinesia and/or severe systolic and certifications to perform POCUS for non-cardiologists dysfunction will be detected just checking the movement of the was published (45). Neurologists have better understood LV. Similarly, mitral stenosis will be assessed by Doppler gradient the functioning of cerebral hemodynamics since they have and mobility of the valves. implemented the use of ultrasonography in their clinical practice. If the function of the LV is normal, we will look at Patients admitted to the Stroke Unit often have hemodynamic the aortic arch as detection of complex aortic plaques is instability. With POCUS we will evaluate the presence of frequent in elderly patients. If we detect a plaque larger than significant ventricular hypertrophy which will guide us not to 4 millimeters size, we will request a TEE during admission hyper hydrate the patient to avoid heart failure. In addition, to evaluate the presence of thrombus related to the complex in those patients in Shock, we can detect the collapse of the plaque. Considering that the sensitivity of POCUS is not high, inferior vena cava to ascertain if the shock is due to heart TEE will be required if the suspicion of embolic stroke is failure. Although very rare, we can also detect pericardial effusion still there. or pericardial tamponade in patients with heart failure or When none of the above provide any data, the size in shock. and characteristics of the LA can be checked. It is worth detecting the existence of A-wave pattern to uncover episodes of paroxysmal AF since the A wave is due to atrial contraction. DISCUSSION Besides, if the volume of the LA is increased we can indicate intensive ambulatory cardiac monitoring to detect Stroke Neurologists are experts in ultrasonography field paroxysmal AF. Thus, we will increase the cost-effectiveness so integrating POCUS into their stroke units makes of POCUS. sense, since 1 out of every 3 patients admitted to the In young patients a saline test with microbubbles can be Stroke Unit requires TTE. In regard to the prevalence performed to detect PFO by POCUS. Furthermore, POCUS of cardioembolic sources a rapid screening protocol can will allow the evaluation of interatrial septal aneurysm, the be drawn up according to the age of the patient and the Eustachian valve and/or the Chiari network in right atrium. presence of vascular risk factors. In TIA patients without Other anomalies such as cardiac tumor and mitral stenosis vascular risk factors POCUS is less cost-effective. However, are very rare so we should not base the cost-effectiveness of the we can perform the POCUS in the first 24 h after stroke POCUS on their detection. in order to shorten diagnostic work-up duration to avoid The yield of POCUS to detect SOE increases when patients overloading care and hospital stay (essential in times with large vessel occlusion were examined in the first hours after of pandemics). the stroke onset (46). FIGURE 1 | Screening protocol for patients with cardioembolic stroke suspicion. POCUS, point of care ultrasound; TEE, transesophageal echocardiogram. Frontiers in Neurology | www.frontiersin.org 3 September 2020 | Volume 11 | Article 1003 Pagola et al. POCUS Enhances Cardioembolic Stroke Detection The detection of SOE with POCUS has some limitations. Patients DISCLOSURE with high clinical suspicion for endocarditis (infective or non- bacterial) or mechanical prosthesis should undergo TEE in all JP is the President of the Spanish Society of Neurosonology, the cases. In addition, since the evaluation of segmental contractility National Coordinator of POCUS certification for neurologists in changes is sometimes challenging, when POCUS is performed Spain and one of the leaders of the Focused Echocardiography in by neurologists it is advisable to seek the counsel of a cardiac Neurosonology group of the European Society of Neurosonology imaging expert (47). and Cerebral Hemodynamics. CONCLUSION AUTHOR CONTRIBUTIONS TTE remains as a useful technique to screen SOE. POCUS JP design and conceptualized the manuscript. CP, JJ, TG-A, JA-S, enhances the detection when performed by neurologists at and CM drafted the manuscript. All authors contributed to the stroke units. article and approved the submitted version. REFERENCES 16. Tsang TS, Abhayaratna WP, Barnes ME, Miyasaka Y, Gersh BJ, Bailey KR, et al. Prediction of cardiovascular outcomes with left atrial size: is 1. Ferro JM. Cardioembolic stroke: an update. Lancet Neurol. (2003) 2:177– volume superior to area or diameter? J Am Coll Cardiol. (2006) 47:1018– 88. doi: 10.1016/S1474-4422(03)00324-7 23. doi: 10.1016/j.jacc.2005.08.077 2. Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et 17. Pagola J, González-Alujas T, Flores A, Muchada M, Rodriguez-Luna D, al. Guidelines for the primary prevention of stroke: a guideline for healthcare Seró L, et al. Left atria strain is a surrogate marker for detection professionals from the American Heart Association/American Stroke of atrial fibrillation in cryptogenic strokes. Stroke. (2014) 45:e164– Association. Stroke. (2011) 42:517–84. doi: 10.1161/STR.0b013e3181fcb238 6. doi: 10.1161/STROKEAHA.114.005540 3. Nakanishi K, Homma S. Role of echocardiography in patients with stroke. J 18. Healey JS, Gladstone DJ, Swaminathan B, Eckstein J, Mundl H, Epstein Cardiol. (2016) 68:91–9. doi: 10.1016/j.jjcc.2016.05.001 AE, et al. Recurrent stroke with rivaroxaban compared with aspirin 4. Morris JG, Duffis EJ, Fisher M. Cardiac workup of ischemic according to predictors of atrial fibrillation: secondary analysis of the stroke: can we improve our diagnostic yield? Stroke. (2009) NAVIGATE ESUS randomized clinical trial. JAMA Neurol. (2019) 76:764– 40:2893–8. doi: 10.1161/STROKEAHA.109.551226 73. doi: 10.1001/jamaneurol.2019.0617 5. Saric M, Armour AC, Arnaout MS, Chaudhry FA, Grimm RA, Kronzon 19. Mooe T, Eriksson P, Stegmayr B. Ischemic stroke after acute I, et al. Guidelines for the use of echocardiography in the evaluation myocardial infarction. A population-based study. Stroke. (1997) of a cardiac source of embolism. J Am Soc Echocardiogr. (2016) 29:1– 28:762–7. doi: 10.1161/01.STR.28.4.762 42. doi: 10.1016/j.echo.2015.09.011 20. Choi JY, Cha J, Jung JM, Seo WK, Oh K, Cho KH, et al. Left ventricular wall 6. Egeblad H, Andersen K, Hartiala J, Lindgren A, Marttila R, Petersen motion abnormalities are associated with stroke recurrence. Neurology. (2017) P, et al. Role of echocardiography in systemic arterial embolism. 88:586–94. doi: 10.1212/WNL.0000000000003588 A review with recommendations. Scand Cardiovasc J. (1998) 21. Jugdutt BI, Sivaram CA. Prospective two-dimensional echocardiographic 32:323–42. doi: 10.1080/14017439850139780 evaluation of left ventricular thrombus and embolism after 7. Doufekias E, Segal AZ, Kizer JR. Cardiogenic and aortogenic brain embolism. acute myocardial infarction. J Am Coll Cardiol. (1989) 13:554– J Am Coll Cardiol. (2008) 51:1049–59. doi: 10.1016/j.jacc.2007.11.053 64. doi: 10.1016/0735-1097(89)90592-5 8. Leung DY, Black IW, Cranney GB, Walsh WF, Grimm RA, Stewart WJ, et 22. Delewi R, Zijlstra F, Piek JJ. Left ventricular thrombus formation al. Selection of patients for transesophageal echocardiography after stroke after acute myocardial infarction. Heart. (2012) 98:1743– and systemic embolic events. Role of transthoracic echocardiography. Stroke. 9. doi: 10.1136/heartjnl-2012-301962 (1995) 26:1820–4. doi: 10.1161/01.STR.26.10.1820 23. Kohsaka S, Sciacca RR, Sugioka K, Sacco RL, Homma S, Di Tullio MR. 9. Giruparajah M, Bosch J, Vanassche T, Mattina K, Connolly SJ, Pater C, et al. Additional impact of electrocardiographic over echocardiographic diagnosis Global survey of the diagnostic evaluation and management of cryptogenic of left ventricular hypertrophy for predicting the risk of ischemic stroke. Am ischemic stroke. Int J Stroke. (2015) 10:1031–6. doi: 10.1111/ijs.12509 Heart J. (2005) 149:181–6. doi: 10.1016/j.ahj.2004.06.006 10. Dietrich CF, Goudie A, Chiorean L, Cui XW, Gilja OH, Dong Y, et al. Point 24. Lechat P, Mas JL, Lascault G, Loron P, Theard M, Klimczac M, et al. Prevalence of care ultrasound: a WFUMB position paper. Ultrasound Med Biol. (2017) of patent foramen ovale in patients with stroke. N Engl J Med. (1988) 43:49–58. doi: 10.1016/j.ultrasmedbio.2016.06.021 318:1148–52. doi: 10.1056/NEJM198805053181802 11. Fonseca AC, Ferro JM. Cryptogenic stroke. Eur J Neurol. (2015) 22:618– 25. Koutroulou I, Tsivgoulis G, Tsalikakis D, Karacostas D, Grigoriadis N, 23. doi: 10.1111/ene.12673 Karapanayiotides T. Epidemiology of patent foramen ovale in general 12. Camen S, Haeusler KG, Schnabel RB. Cardiac imaging after population and in stroke patients: a narrative review. Front Neurol. (2020) ischemic stroke: echocardiography, CT, or MRI? Herz. (2019) 11:281. doi: 10.3389/fneur.2020.00281 44:296–303. doi: 10.1007/s00059-019-4803-x 26. Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and 13. Iwataki M, Takeuchi M, Otani K, Kuwaki H, Haruki N, Yoshitani H, et stroke: a meta-analysis of case-control studies. Neurology. (2000) al. Measurement of left atrial volume from transthoracic three-dimensional 55:1172–9. doi: 10.1212/WNL.55.8.1172 echocardiographic datasets using the biplane Simpson’s technique. J Am Soc 27. Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff Echocardiogr. (2012) 25:1319–26. doi: 10.1016/j.echo.2012.08.017 L, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets 14. Pritchett AM, Jacobsen SJ, Mahoney DW, Rodeheffer RJ, Bailey KR, Redfield after stroke. N Engl J Med. (2017) 377:1011–21. doi: 10.1056/NEJMoa170 MM. Left atrial volume as an index of left atrial size: a population-based study. 5915 J Am Coll Cardiol. (2003) 41:1036–43. doi: 10.1016/S0735-1097(02)02981-9 28. Schuchlenz HW, Saurer G, Weihs W, Rehak P. Persisting eustachian valve in 15. Jordan K, Yaghi S, Poppas A, Chang AD, Mac Grory B, Cutting S, et al. adults: relation to patent foramen ovale and cerebrovascular events. J Am Soc Left atrial volume index is associated with cardioembolic stroke and atrial Echocardiogr. (2004) 17:231–3. doi: 10.1016/j.echo.2003.12.003 fibrillation detection after embolic stroke of undetermined source. Stroke. 29. Martínez-Quintana E, Rodríguez-González F. Chiari network and paradoxical (2019) 50:1997–2001. doi: 10.1161/STROKEAHA.119.027235 embolism. Rev Esp Cardiol. (2015) 68:273. doi: 10.1016/j.rec.2014.09.018 Frontiers in Neurology | www.frontiersin.org 4 September 2020 | Volume 11 | Article 1003 Pagola et al. POCUS Enhances Cardioembolic Stroke Detection 30. Smilowitz NR, Subashchandran V, Berger JS. Atrial septal defect and the risk 41. Izumo M, Akashi YJ. Role of echocardiography for takotsubo of ischemic stroke in the perioperative period of noncardiac surgery. Am J cardiomyopathy: clinical and prognostic implications. Cardiovasc Diagn Cardiol. (2019) 124:1120–4. doi: 10.1016/j.amjcard.2019.06.030 Ther. (2018) 8:90–100. doi: 10.21037/cdt.2017.07.03 31. Ntaios G, Hart RG. Embolic stroke. Circulation. (2017) 136:2403– 42. Captur G, Nihoyannopoulos P. Left ventricular non-compaction: genetic 5. doi: 10.1161/CIRCULATIONAHA.117.030509 heterogeneity, diagnosis and clinical course. Int J Cardiol. (2010) 140:145– 32. Amarenco P, Cohen A, Hommel M, Moulin T, Leys D, Bousser 53. doi: 10.1016/j.ijcard.2009.07.003 MG, et al. Atherosclerotic disease of the aortic arch as a risk 43. Kraft P, Fleischer A, Wiedmann S, Rücker V, Mackenrodt D, Morbach factor for recurrent ischemic stroke. N Engl J Med. (1996) C, et al. Feasibility and diagnostic accuracy of point-of-care handheld 334:1216–21. doi: 10.1056/NEJM199605093341902 echocardiography in acute ischemic stroke patients - a pilot study. BMC 33. Kronzon I, Tunick PA. Aortic atherosclerotic disease and stroke. Neurol. (2017) 17:159. doi: 10.1186/s12883-017-0937-8 Circulation. (2006) 114:63–75. doi: 10.1161/CIRCULATIONAHA.105.59 44. Pagola J, González-Alujas T, Muchada M, Teixidó G, Flores A, De Blauwe S, et 3418 al. Stroke echoscan protocol: a fast and accurate pathway to diagnose embolic 34. Seckeler MD, Hoke TR. The worldwide epidemiology of acute strokes. J Neuroimaging. (2015) 25:365–9. doi: 10.1111/jon.12139 rheumatic fever and rheumatic heart disease. Clin Epidemiol. (2011) 45. Pérez de Isla L, Díaz Sánchez S, Pagola J, García de Casasola Sánchez G, 3:67–84. doi: 10.2147/CLEP.S12977 López Fernández T, Sánchez Barrancos IM, et al. Consensus document of the 35. Vilacosta I, Graupner C, San Román JA, Sarriá C, Ronderos SEMI, semFYC, SEN, and SEC on focused cardiac ultrasound in Spain. Rev R, Fernández C, et al. Risk of embolization after institution of Esp Cardiol. (2018) 71:935–40. doi: 10.1016/j.recesp.2018.05.027 antibiotic therapy for infective endocarditis. J Am Coll Cardiol. (2002) 46. Juega J, Pagola J, Gonzalez-Alujas T, Rodriguez-Luna D, Rubiera M, 39:1489–95. doi: 10.1016/S0735-1097(02)01790-4 Rodriguez-Villatoro N, et al. Screening of embolic sources by point-of-care 36. Reisner SA, Brenner B, Haim N, Edoute Y, Markiewicz W. Echocardiography ultrasound (POCUS) in the acute phase of ischemic stroke. Ultrasound Med in nonbacterial thrombotic endocarditis: from autopsy to clinical entity. Biol. (2020) 46:2173–80. doi: 10.1016/j.ultrasmedbio.2020.05.009 J Am Soc Echocardiogr. (2000) 13:876–81. doi: 10.1067/mje.2000.10 47. Cullen MW, Blauwet LA, Vatury OM, Mulvagh SL, Behrenbeck 6070 TR, Scott CG, et al. Diagnostic capability of comprehensive 37. Rodriguez CJ, Bartz TM, Longstreth WT, Kizer JR, Barasch E, Lloyd-Jones handheld vs transthoracic echocardiography. Mayo Clin Proc. (2014) DM, et al. Association of annular calcification and aortic valve sclerosis with 89:790–8. doi: 10.1016/j.mayocp.2013.12.016 brain findings on magnetic resonance imaging in community dwelling older adults: the cardiovascular health study. J Am Coll Cardiol. (2011) 57:2172– Conflict of Interest: The authors declare that the research was conducted in the 80. doi: 10.1016/j.jacc.2011.01.034 absence of any commercial or financial relationships that could be construed as a 38. Chevalier B, Reant P, Laffite S, Barandon L. Spontaneous fistulization of a potential conflict of interest. caseous calcification of the mitral annulus: an exceptional cause of stroke. Eur J Cardiothorac Surg. (2011) 39:e184–5. doi: 10.1016/j.ejcts.2011.01.038 Copyright © 2020 Pagola, Pagola, Juega, González-Alujas, Alvarez-Sabin and 39. Reynen K. Cardiac myxomas. N Engl J Med. (1995) 333:1610– Molina. This is an open-access article distributed under the terms of the Creative 7. doi: 10.1056/NEJM199512143332407 Commons Attribution License (CC BY). The use, distribution or reproduction in 40. Sun JP, Asher CR, Yang XS, Cheng GG, Scalia GM, Massed AG, et al. other forums is permitted, provided the original author(s) and the copyright owner(s) Clinical and echocardiographic characteristics of papillary fibroelastomas: are credited and that the original publication in this journal is cited, in accordance a retrospective and prospective study in 162 patients. Circulation. (2001) with accepted academic practice. No use, distribution or reproduction is permitted 103:2687–93. doi: 10.1161/01.CIR.103.22.2687 which does not comply with these terms. Frontiers in Neurology | www.frontiersin.org 5 September 2020 | Volume 11 | Article 1003